Aim: To determine platelet activating factor (PAF) receptor expression in cirrhotic hepatic stellate cells.
Methods: Hepatic stellate cells, isolated from the livers of control and CCl(4)-induced cirrhotic rats, were placed in serum-free medium after overnight culture. We determined the PAF receptor in hepatic stellate cells by saturation binding technique and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the effects of PAF and its antagonist BN52021 on prostaglandin E(2) (PGE(2)) release by stellate cells.
Results: Scatchard analysis indicated the presence of PAF receptor with dissociation constant (Kd) of 4.66 nmol/L and maximum binding capacity (Bmax) of 24.65 fmol/microg in cirrhotic stellate cells. Compared with the control, the maximum PAF binding capacity increased significantly (Bmax: 24.65 +/- 1.96 fmol/microg. DNA, R = 0.982 vs 5.74 +/- 1.55 fmol/microg. DNA, R = 0.93; P < 0.01), whereas receptor affinity had no significant difference (Kd of 4.66 +/- 0.33 nmol/L for the cirrhosis and 3.51 +/- 0.26 nmol/L for the control; P > 0.05). Consistent with the receptor binding data, the mRNA expression of PAF receptor was increased significantly in cirrhotic stellate cells. PAF in a concentration-dependent manner induced PGE(2) synthesis in cirrhotic hepatic stellate cells, but the effects were blocked significantly by BN52021.
Conclusion: Cirrhosis sensitizes hepatic stellate cells to PAF by elevating its receptor level and hepatic stellate cells maybe potential effectors of PAF induced portal hypertension.